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Title: Dephosphorylation of nucleophosmin by PP1β facilitates pRB binding and consequent E2F1-dependent DNA repair
Authors: Lin, Chiao Yun
Tan, Bertrand Chin-Ming
Liu, Hsuan
Shih, Chii-Jiun
Chien, Kun-Yi
Lin, Chih-Li
Yung, Benjamin Yat-ming
Subjects: Cell line
DNA damage
DNA repair
Dose-response relationship, radiation
E2F1 transcription factor/genetics
E2F1 transcription factor/metabolism
E2F1 transcription factor/physiology
Gene expression regulation/radiation effects
Mutation, missense/physiology
Nuclear proteins/genetics
Nuclear proteins/metabolism
Nuclear proteins/physiology
Protein binding
Protein phosphatase 1/genetics
Protein phosphatase 1/metabolism
Protein phosphatase 1/physiology
Retinoblastoma protein/genetics
Retinoblastoma protein/metabolism
Retinoblastoma protein/physiology
Time factors
Ultraviolet rays/adverse effects
Issue Date: 15-Dec-2010
Publisher: The American Society for Cell Biology
Source: Molecular Biology of the Cell, 15 Dec. 2010, v. 21, no. 24, p. 4409-4417.
Abstract: Nucleophosmin (NPM) is an important phosphoprotein with pleiotropic functions in various cellular processes. Although phosphorylation has been postulated as an important functional determinant, possible regulatory roles of this modification on NPM are not fully characterized. Here, we find that NPM is dephosphorylated on various threonine residues (Thr199 and Thr234/237) in response to UV-induced DNA damage. Further experiments indicate that the serine/threonine protein phosphatase PP1β is a physiological NPM phosphatase under both the genotoxic stress and growth conditions. As a consequence, NPM in its hypophosphorylated state facilitates DNA repair. Finally, our results suggest that one possible mechanism of this protective response lies in enhanced NPM-retinoblastoma tumor suppressor protein (pRB) interaction, leading to the relief of the repressive pRB–E2F1 circuitry and the consequent transcriptional activation of E2F1 and several downstream DNA repair genes. Thus, this study unveils a key phosphatase of NPM and highlights a novel mechanism by which the PP1β–NPM pathway contributes to cellular DNA damage response.
Rights: © 2010 C. Y. Lin et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution– Noncommercial–Share Alike 3.0 Unported Creative Commons License (
The following article appeared in Lin, C. Y. et al., Molecular Biology of the Cell, v. 21, no. 24, p. 4409-4417 and may be found at
Type: Journal/Magazine Article
DOI: 10.1091/mbc.E10-03-0239
ISSN: 1059-1524
Appears in Collections:HTI Journal/Magazine Articles

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